[owk9688]

Hi guys,

Im TBS protecting a phenyl alcohol with TBSCl and Triethylamine in DCM with DMAP acting as a catalyst. The paper I'm using as precedent gives a workup using an aqueous Ammonium Chloride wash followed by distilled water washes. I tried looking online but I couldnt figure out definitively what the purpose is for using the NH₄Cl wash. Is it simply a milder version of an acidic wash (to remove any excess TEA into the aqueous layer maybe)? I know Ammonium is only a weak acid but if thats its only purpose could I just use a very dilute HCl wash instead? My lab doesnt have NH₄Cl so I'm just wondering if I could use a different wash/trying to understand why Ammonium Chloride washes are used in general.

Thanks for any help 

[wildfyr]

You're exactly right, its a weak acid that won't quickly cleave TBS, but allows you to protonate your bases and get them into the water layer. HCl can hydrolyze your silyl ether, though TBS is pretty tough and if its low concentration HCl for a short time you shouldnt lose much yield. You could always make your own from ammonia solution and HCl.

That said, I've always had excellent results 1:1.1:2.2 eq of alcohol:TBS-Cl:imidazole in DCM, THF or DMF at RT, overnight under N2. EJ Corey in the 70's found that imidazole is uniquely excellent at TBS protection. The one catch at those ratios is that sometimes you get a little TBS dimer and have to distill or run a hexane column. In your case though, you can just do 1:0.95:2 ratio, and leftover phenol will be water soluble. Should get very high yield, and the workup is just water since imidazole is quite soluble in water.

I'll go ahead an toot my own horn with the procedure in my supporting info http://onlinelibrary.wiley.com/doi/10.1002/anie.201506253/abstract

[owk9688]

Thank you so much for the explanation and tip! I'll look into ordering or finding out if we have any Imidazole in stock.

[wildfyr]

I just looked at your post again, dont do the underequivalency if you phenol isnt water soluble